Abstract | PURPOSE: METHODS: We clinically scored the uveitis over time in B10.RIII, C57BL/6, and melanocortin 5 receptor knock-out (MC5r((-/-))) mice with experimental autoimmune uveitis (EAU) that were conjunctively injected with a naked DNA plasmid encoding ACTH1-17 at the time of EAU onset and three days later. The post-EAU retina histology of plasmid injected eyes was examined, and post-EAU concentrations of alpha-MSH in aqueous humor was assayed by ELISA. RESULTS: The subconjunctival injection of ACTH1-17 plasmid augmented the concentration of alpha-MSH in the aqueous humor of all post-EAU mice. The injection of ACTH1-17 suppressed the severity of EAU in the B10.RIII and C57BL/6 mice but the MC5r((-/-)) mice. In all the models of EAU, the ACTH1-17 injection helped to preserve the structural integrity of the retina; however, post-EAU aqueous humor was not immunosuppressive. CONCLUSIONS: The subconjunctival injection of the alpha-MSH expression vector ACTH1-17 plasmid is effective in suppressing EAU. The suppressive activity is dependent on MC5r expression, and possibly works though alpha-MSH antagonism of inflammation than on alpha-MSH directly modulating immune cells. The results suggest that an effective therapy for uveitis could include a gene therapy approach based on delivering alpha-MSH.
|
Authors | D J Lee, D J Biros, A W Taylor |
Journal | International immunopharmacology
(Int Immunopharmacol)
Vol. 9
Issue 9
Pg. 1079-86
(Aug 2009)
ISSN: 1878-1705 [Electronic] Netherlands |
PMID | 19426838
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Anti-Inflammatory Agents
- Eye Proteins
- Peptide Fragments
- Receptors, Melanocortin
- Retinol-Binding Proteins
- Vaccines, DNA
- interstitial retinol-binding protein
- melanocortin 5 receptor
- alpha-MSH
- Adrenocorticotropic Hormone
- Freund's Adjuvant
- ACTH (1-17)
|
Topics |
- Adrenocorticotropic Hormone
(genetics)
- Animals
- Anti-Inflammatory Agents
(administration & dosage)
- Aqueous Humor
- Autoimmune Diseases
(genetics, immunology, therapy)
- Eye Proteins
(immunology)
- Freund's Adjuvant
- Genetic Therapy
- Humans
- Immunosuppression Therapy
- Injections
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- Models, Animal
- Peptide Fragments
(genetics, immunology)
- Plasmids
- Protein Engineering
- Receptors, Melanocortin
(deficiency)
- Retina
(immunology, metabolism, pathology)
- Retinol-Binding Proteins
(immunology)
- Uveitis
(genetics, immunology, therapy)
- Vaccines, DNA
(administration & dosage)
- alpha-MSH
(genetics, immunology, metabolism)
|